Propargyl esters coupling

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

Other indole syntheses of this type include the iridium-catalyzed hydrogen transfer of amine-substituted benzylic alcohols (130L3876), the intramolecular dehydrative coupling of tertiary amines with ketones (13OL6018), and the sequential alkylation/cyclization/isomerization of 3-(o-tri luoroacetamidoaryl)-l-propargylic esters (13T9494). 

Scheme 3.44b).Another efficient palladium-catalyzed intramolecular carbopalladation-cyclization cascade toward tetra- and pentacyclic N-fused heterocycles was developed in 2010. This transformation proceeds via the palladium-catalyzed coupling of aryl halides with internal propargylic esters or ethers followed by a 5-endo-dig cyclization leading to polycyclic pyrrolo-heterocycles in moderate to excellent yields (Scheme 3.44c). 

The Stille adduct of 2-bromothiophene and l-ethoxy-2-tributyl-n-stannylethene or 1-ethoxy-l-tri-n-butylstannylethene is a masked thienyl aldehyde or a masked ketone, respectively [77-80]. Vinylstannane 93, derived exclusively as the -isomer from hydrostannation of bis(trimethyl-silyl)propargyl amine (92), was coupled with 2-bromothiophene to form ( )-cinnamyl amine 94 upon acidic hydrolysis [81, 82], In another case, stereoisomerically pure phenyl ( )-2-tributylstannyl-2-alkenoate 95, arising from Pd-mediated hydrostannation of phenyl ( )-2-alkynoate, was joined with 2-iodothiophene to deliver the stereodefmed trisubstituted a,p-unsaturated ester 96 [83, 84],... 

In other examples, also involving propargyl carbonates, the parent derivative 86 was first coupled with 87 - obtained by reaction of 5-octyne with the titanium diiso-propoxide - propene complex at -50 °C, providing the titanated vinylallene 88, which on hydrolysis furnished the vinylallenes 89 in good yield [29]. Carbonate 90 in the presence of a Pd° catalyst readily decarboxylated and yielded the allenylpalladium intermediate 91, which could be coupled with various vinyl derivatives to afford the vinylallenes 92. Since X represents a functional group (ester, acetyl), functionalized vinylallenes are available by this route [30]. 

Alternatively, bromo trienyne 66, prepared by the Wittig reaction of TMS-capped propargyl ylide with , -5-bromo-2,4-pentadienal, could be coupled with dienyl zinc reagent 67, as illustrated in equation 3657. Subsequent desilylation followed by treatment with trimethyl aluminum in the presence of catalytic Cp2ZrCl2 afforded the alane of tetraenyne 68 which, on exposure to chloroformate, gave essentially all- polyene ester 69. 

The coupling reaction of a-keto esters with allyl, propargyl, and allenyl halides using indium metal in aqueous solvents affords a-hydroxy-y,<5-unsaturated esters (Equation (28)).197,198 1,3-Dicarbonyl compounds undergo efficient carbonyl allylation reactions in an aqueous medium through a Barbier-type reaction (Equation (29)). The reaction is general and a variety of 1,3-dicarbonyls has been alkylated using allyl bromide or allyl chloride in conjunction with indium.199... 

A related one-pot three component coupling reaction leading to allyli-dene tetrahydrofuran derivatives 80 and which combines a conjugate addition of a propargyl alcohol with an activated olefin and an in situ palladium-catalyzed carbopalladation-cyclization in the presence of a large excess of allyl chloride has been recently developed by Lu and Iiu (Scheme 31) [77]. The cyclization process is here initiated by addition of a catalytic amount of Pd(OAc)2 and in marked contrast with the above-discussed reactions, a catalytic cycle involving divalent palladium proceeds in the reaction. In this process, the ester enolate formed in the Michael addition undergoes... 

Allyl)Fp complexes are also subject to attack, at C-3, by radicals. The mechanism of allylic transposition of ()] -allyl)Fp complexes, as well as the mechanism of phosphite substitution for CO, has been ascribed to attack by Cp(CO)(L)Fe- on the original Fp-aUyl. The reaction of (12) with CCI4 proceeds by a radical chain mechanism, ultimately between CCI3 and the Fp-allyl. The substitution of a-halo ketones and esters most likely proceeds similarly. A radical cation coupling mechanism has been proposed for the dimerization of (jj -allyl)Fp and (j7 -propargyl)Fp complexes. ... 

Only the 5-carbomethoxy isomer (169c) displayed high affinity and activity at muscarinic receptors coupled to phosphoinositide metabolism in rat cortex. Evaluation of other alkyl esters (170a-c) of the 5-carboxylic acid revealed that only the propargyl derivative (170c) retained substantial agonist activity. 

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